1. Field of the Invention
The present invention relates to daunomycin analogues (i.e., 14-alkoxy (or aryloxy) daunomycins), a method for making them, certain novel intermediates which are used in the method for making them, methods for making the intermediates and methods of using the daunomycin analogues in treating certain amamalian tumors.
2. The Prior Art
Daunomycin as well as its aglycone - daunomycinone are, of course, known compounds. Moreover, 14-bromodaunomycinone is also a known compound.
The compounds according to the invention, as will appear below, are .alpha.-alkoxy (or aryloxy) ketones inasmuch as they possess the ##STR3##
It has long been known from the literature (S. Patai. The Chemistry of Ether Linkage, 480 (1976; Interscence Publishers)) that .alpha.-alkoxyketones can be prepared from the relatively inaccessible diazoketones by a rather complicated overall process. Possible alternative methods for producing such compounds, such as by the nucleophilic substitution of a halogen atom in an .alpha.-haloketone by an alkoxyl anion, however, yield different products, namely epoxyethers, .alpha.-hydroxyketals and .alpha.-hydroxyketones (J. Am. Chem. Soc. 74, 618 (1952) and ibid 78 (1956)), or compounds resulting from Favorsky rearrangement (Organic Reactions 11, 261 (1960)).
Moreover, it has been ascertained that 14-bromodaunomycinone does not react directly with alcohols in the presence of silver salts or silver oxide.